AD and VaD exhibit such different profiles of organ and vascular damage as well as of hypertension and DM that they clearly point toward different pathogenic origin with low likelihood of shared risk factors.

Background: Research concerning the potential roles of cardiovascular disease (CaVD) and diabetes mellitus (DM) as risk factors for Lewy body disease (LBD) is limited. These disorders are, however, established risk factors for vascular dementia (VaD) and have been proposed as risk factors for Alzheimer's disease (AD). Objective: The aim of this study was to investigate the prevalence of CaVD and DM in LBD and compare the results with previous findings in cases with AD, VaD, and mixed AD-VaD (MD). Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 2001-2018 were analyzed. All cases with a complete neuropathological diagnosis of LBD were selected, not distinguishing between subjects with clinical Parkinson disease dementia and dementia with Lewy bodies, on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through the patients' medical records and the Swedish National Diabetes Register (NDR) and compared with those of the AD, VaD, and MD cases. Results: In LBD, there was less CaVD, significantly less DM (p = 0.002) and likewise significantly less hypertension (p < 0.001) than in VaD. The results of the LBD group were consistent with the results of the AD group. Conclusion: Our findings of a low prevalence of CaVD and CaVD risk factors in LBD and in AD argue against the association between these risk factors and their contribution to the development of neurodegenerative diseases.

Background: Alpha-synucleinopathies (AS) are characterized by pathologic aggregations of alpha-synuclein (α-syn) in the central nervous system, and comprise dementia with Lewy bodies, Parkinson’s disease, and multiple system atrophy. Previous studies on AS have reported findings of α-syn pathology in the peripheral nervous system of multiple organs, including the heart. Objective: The aim of this study was to further investigate and confirm the presence of cardiac α-syn in AS compared to other major neurocognitive disorders in a neuropathologically confirmed cohort. Methods: All deceased patients with performed autopsy and with neuropathologically confirmed AS at the Clinical Department of Pathology in Lund 2010–May 2021 were evaluated for inclusion. Cases with insufficiently sampled cardiac tissue or only limited neuropathological investigation were excluded. An age-matched group of individuals with other neurodegenerative diseases, having no α-syn in the CNS, served as controls. In total, 68 AS and 32 control cases were included in the study. Immunohistochemistry for detection of cardiac α-syn aggregates was performed. Results: The AS group had a significantly higher prevalence of cardiac α-syn pathology (p≤0.001) than the control group, 82% and 0%, respectively. Conclusion: This study confirms the association between AS and the presence of cardiac α-syn in a neuropathologically confirmed cohort. This motivates further research on potential pathophysiological effects on cardiac function in AS patients.

On page 1253, the right column, line 6 from the bottom, the text gives [58] as a reference: "In 2013, the prevalence of DM was reported to be 15.6% among the normal Swedish population in individuals >65 years [58], which is an age group in proximity to our study group (81 years, SD 9

The purpose of this study was to investigate the cause of death in subjects with α-synucleinopathies (ASs) and the confirmed presence of cardiac α-synuclein (α-syn), compared to non-AS disorders in a neuropathologically confirmed cohort. In total, 78 neuropathologically confirmed AS cases positive for cardiac α-syn were included in the study. Individuals with other neurocognitive diseases, having no α-syn in the brainstem or above, nor in cardiac nerves, served as controls (n = 53). Data regarding the cause of death, cardiac α-syn, pathological cardiac findings, and cardio- and cerebrovascular disease were assembled from autopsy reports and medical records. In the AS group, there was a significantly higher prevalence of sudden cardiac death ([SCD]; n = 40, 51.3%) compared to the control group (n = 12, 22.6%, p &lt; 0.001). No statistically significant differences between the groups were reported regarding other cardiac conditions on autopsy or regarding cardio- and cerebrovascular disease from the medical records. The most prevalent cause of death in the AS group was SCD, which differed significantly from the control group. This suggests that α-syn deposits in cardiac nerves may cause lethal alterations in cardiac function, warranting further research.